A tagging polymorphism in fat mass and obesity-associated () gene is associated with sepsis status in children.

Introduction: Sepsis is one of the most common causes of death in patients admitted to intensive care units (ICUs). The development of sepsis is significantly influenced by genetic predisposition. In this study, we highlight a potential association between a variant of the fat mass and obesity-associated () gene and risk of sepsis in children and adolescents.

Cryo-EM structures of a synthetic antibody against 22 kDa claudin-4 reveal its complex with enterotoxin.

Claudins are a family of ∼25 kDa membrane proteins that integrate into tight junctions to form molecular barriers at the paracellular spaces between endothelial and epithelial cells. Humans have 27 subtypes, which homo- and hetero-oligomerize to impart distinct properties and physiological functions to tissues and organs. As the structural and functional backbone of tight junctions, claudins are attractive targets for therapeutics capable of modulating tissue permeability to deliver drugs or treat disease.

Conformation-specific Synthetic Antibodies Discriminate Multiple Functional States of the Ion Channel CorA.

CorA, the primary magnesium ion channel in prokaryotes and archaea, is a prototypical homopentameric ion channel that undergoes ion-dependent conformational transitions. CorA adopts five-fold symmetric non-conductive states in the presence of high concentrations of Mg, and highly asymmetric flexible states in its complete absence. However, the latter were of insufficient resolution to be thoroughly characterized.

Conformation-specific synthetic antibodies discriminate multiple functional states of the ion channel CorA.

CorA, the primary magnesium ion channel in prokaryotes and archaea, is a prototypical homopentameric ion channel that undergoes ion-dependent conformational transitions. CorA adopts five-fold symmetric non-conductive states in the presence of high concentrations of Mg , and highly asymmetric flexible states in its complete absence. However, the latter were of insufficient resolution to be thoroughly characterized.

Stimulant abuse as a coping strategy-Forensic and criminal consequences of stimulant abuse for neuroenhancement.

Pharmacological neuroenhancement (PN) describes the use of divergent psychoactive substances to enhance mental performance (cognition) without medical need. This kind of substance abuse takes place predominantly in stressful situations. Users implicitly-or even explicitly-describe this kind of drug abuse to be a coping strategy.

Development, structure, and mechanism of synthetic antibodies that target claudin and Clostridium perfringens enterotoxin complexes.

Strains of Clostridium perfringens produce a two-domain enterotoxin (CpE) that afflicts humans and domesticated animals, causing prevalent gastrointestinal illnesses. CpE's C-terminal domain (cCpE) binds cell surface receptors, followed by a restructuring of its N-terminal domain to form a membrane-penetrating β-barrel pore, which is toxic to epithelial cells of the gut. The claudin family of membrane proteins are known receptors for CpE and also control the architecture and function of cell-cell contacts (tight junctions) that create barriers to intercellular molecular transport.

Structures of atypical chemokine receptor 3 reveal the basis for its promiscuity and signaling bias.

Both CXC chemokine receptor 4 (CXCR4) and atypical chemokine receptor 3 (ACKR3) are activated by the chemokine CXCL12 yet evoke distinct cellular responses. CXCR4 is a canonical G protein-coupled receptor (GPCR), whereas ACKR3 is intrinsically biased for arrestin. The molecular basis for this difference is not understood.

Quaternary structure independent folding of voltage-gated ion channel pore domain subunits.

Every voltage-gated ion channel (VGIC) has a pore domain (PD) made from four subunits, each comprising an antiparallel transmembrane helix pair bridged by a loop. The extent to which PD subunit structure requires quaternary interactions is unclear. Here, we present crystal structures of a set of bacterial voltage-gated sodium channel (BacNa) 'pore only' proteins that reveal a surprising collection of non-canonical quaternary arrangements in which the PD tertiary structure is maintained.

COVID-19 associated Paediatric Inflammatory Multisystem Syndrome (PIMS) in children.

The clinical course of the SARS-CoV-2 virus infection (COVID-19 disease) in paediatric patients is predominantly mild. However, in a small percentage of paediatric patients, the COVID-19 could lead to the development of with the Paediatric Inflammatory Multisystem Syndrome (PIMS) presenting as high fever, gastrointestinal symptoms, neurological symptomatology and even as multiorgan dysfunction. These three cases represent the first published report of critically ill paediatric patients with PIMS in the Czech Republic.

Unvaccinated child tetanus from nasal toy battery.

We present the case report of an unvaccinated Czech child with tetanus. The child had not received any vaccines due to its parent's refusal. The disease originated from the wound in the nose caused by a small flat battery.

Structural delineation and phase-dependent activation of the costimulatory CD27:CD70 complex.

CD27 is a tumor necrosis factor (TNF) receptor, which stimulates lymphocytes and promotes their differentiation upon activation by TNF ligand CD70. Activation of the CD27 receptor provides a costimulatory signal to promote T cell, B cell, and NK cell activity to facilitate antitumor and anti-infection immunity. Aberrant increased and focused expression of CD70 on many tumor cells renders CD70 an attractive therapeutic target for direct tumor killing.

Effect of Heme Oxygenase-1 on Melanoma Development in Mice-Role of Tumor-Infiltrating Immune Cells.

Objective: Heme oxygenase-1 (HO-1) is a cytoprotective, proangiogenic and anti-inflammatory enzyme that is often upregulated in tumors. Overexpression of HO-1 in melanoma cells leads to enhanced tumor growth, augmented angiogenesis and resistance to anticancer treatment. The effect of HO-1 in host cells on tumor development is, however, hardly known.

Biogas residue parameterization for soil organic matter modeling.

A variety of biogas residues (BGRs) have been used as organic fertilizer in agriculture. The use of these residues affects the storage of soil organic matter (SOM). In most cases, SOM changes can only be determined in long-term observations.

Final Report on the Key Comparison CCM.P-K4.2012 in Absolute Pressure from 1 Pa to 10 kPa.

The report summarizes the Consultative Committee for Mass (CCM) key comparison CCM.P-K4.2012 for absolute pressure spanning the range of 1 Pa to 10 000 Pa.

Cryo-EM Structures of the Magnesium Channel CorA Reveal Symmetry Break upon Gating.

CorA, the major Mg(2+) uptake system in prokaryotes, is gated by intracellular Mg(2+) (KD ∼ 1-2 mM). X-ray crystallographic studies of CorA show similar conformations under Mg(2+)-bound and Mg(2+)-free conditions, but EPR spectroscopic studies reveal large Mg(2+)-driven quaternary conformational changes. Here, we determined cryo-EM structures of CorA in the Mg(2+)-bound closed conformation and in two open Mg(2+)-free states at resolutions of 3.

Conformational Chaperones for Structural Studies of Membrane Proteins Using Antibody Phage Display with Nanodiscs.

A major challenge in membrane biophysics is to define the mechanistic linkages between a protein's conformational transitions and its function. We describe a novel approach to stabilize transient functional states of membrane proteins in native-like lipid environments allowing for their structural and biochemical characterization. This is accomplished by combining the power of antibody Fab-based phage display selection with the benefits of embedding membrane protein targets in lipid-filled nanodiscs.

A YidC-like Protein in the Archaeal Plasma Membrane.

Cells possess specialized machinery to direct the insertion of membrane proteins into the lipid bilayer. In bacteria, the essential protein YidC inserts certain proteins into the plasma membrane, and eukaryotic orthologs are present in the mitochondrial inner membrane and the chloroplast thylakoid membrane. The existence of homologous insertases in archaea has been proposed based on phylogenetic analysis.

Phage display selections for affinity reagents to membrane proteins in nanodiscs.

Phage display selections generate high-affinity synthetic reagents that can be used as tools in structural characterization of membrane proteins. Currently, most selection protocols are performed with membrane protein targets in detergents. However, there are numerous technical issues associated with this, primarily that detergents are poor mimics of the native lipid environment.

Effects of heme oxygenase-1 on induction and development of chemically induced squamous cell carcinoma in mice.

Heme oxygenase-1 (HO-1) is an antioxidative and cytoprotective enzyme, which may protect neoplastic cells against anticancer therapies, thereby promoting the progression of growing tumors. Our aim was to investigate the role of HO-1 in cancer induction. Experiments were performed in HO-1(+/+), HO-1(+/-), and HO-1(-/-) mice subjected to chemical induction of squamous cell carcinoma with 7,12-dimethylbenz[a]anthracene and phorbol 12-myristate 13-acetate.

A conserved archaeal pathway for tail-anchored membrane protein insertion.

Eukaryotic tail-anchored (TA) membrane proteins are inserted into the endoplasmic reticulum by a post-translational TRC40 pathway, but no comparable pathway is known in other domains of life. The crystal structure of an archaebacterial TRC40 sequence homolog bound to ADP•AlF(4) (-) reveals characteristic features of eukaryotic TRC40, including a zinc-mediated dimer and a large hydrophobic groove. Moreover, archaeal TRC40 interacts with the transmembrane domain of TA substrates and directs their membrane insertion.

Simple spectrophotometric determination of Fe in oxalate and HCl soil extracts.

We describe a spectrophotometric method to determine the sum of Fe(II) plus Fe(III) in HCl and oxalate extracts. The principle of the method is to reduce Fe(III) by ascorbate in near-neutral solution and to sequester the Fe(II) formed as a tri-ferrozine complex, which is then determined photometrically at 562 nm. Because the complex is stable, the reaction is irreversible and complete.